CpG-ODN-based immunotherapy is effective in controlling the growth of metastasized tumor cells.
Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG-ODN) act as potent immune stimulators by activating innate immunity through toll-like receptor 9. These immunomodulatory effects of CpG-ODN have been reported to be associated with anti-tumor immunity. In this study, we used a murine B16F10 melanoma model and a CT26 colon cancer model to assess whether CpG-ODN-based immunotherapy was effective in inhibiting tumor cells that have already metastasized to distant organs. Systemic administration of CpG-ODN after melanoma cell injection resulted in a significant inhibition of pulmonary colonization. When CpG-ODN was administered after tumor cell injection, it also inhibited pulmonary metastasis of the tumor cells, albeit to a lesser degree in the latter case. Systemic administration of CpG-ODN after subcutaneous inoculation of CT26 colon cancer cells diminished pulmonary metastasis from the primary tumor sites. Additionally, CpG-ODN also inhibited the growth of pulmonary colonization of the colon tumor cells when CpG-ODN was administered after the primary tumors had been surgically removed. These data indicate that CpG-ODN was effective in inhibiting pulmonary metastasis of the B16F10 melanoma and CT26 colon cancer cells, as well as the growth of metastasized tumor cells. Our results suggest that CpG-ODN-based immunotherapy may be beneficial in controlling micrometastasis after surgery in clinical settings.
Kim
Han-A
HA
Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Gwangju 500-757, Republic of Korea.
Ko
Hyun-Mi
HM
Ju
Hye-Won
HW
Kim
Kyoung-Jin
KJ
Roh
Si-Gyun
SG
Lee
Hern-Ku
HK
Im
Suhn-Young
SY
D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000627:therapeutic use*; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides